The bombesin-like peptides comprise a large family of peptides originally characterized in amphibians, then later found to be widely distributed in mammals. CNS administration of bombesin to rats has potent effects on appetite, body temperature, grooming, heart rate, and GI function. Two mammalian bombesin-like peptides, gastrin-releasing peptide (GRP) and neuromedin B (NMB) have been characterized to date. At present, three mammalian bombesin-like peptide receptors have been characterized; the GRP receptor (also known as the bombesin BB2 receptor), the NMB receptor (also known as the BB1 receptor) and a third, orphan receptor whose ligand is unknown, designated the BRS-3 receptor or BB3 receptor. These known receptors cannot, however, explain all of bombesin=s CNS effects, particularly bombesin=s effects on body temperature and grooming. This suggests that other bombesin receptor subtypes remain to be characterized. Our laboratory has now characterized two new recep tors related to the bombesin receptors. These receptors are very highly expressed in the CNS. These receptors have been designated GPCR-CNS1 and GPCR-CNS2. In the CNS, expression is primarily found in glia. Preliminary results suggest that each receptor is preferentially localized in different glial subtypes. Unlike the GRP receptor, these receptors are not present in fetal monkey lung. FUNDING SOURCE NIH NS35580 PUBLICATIONS Leng N, Gu GB, Simerly RB, Spindel ER. Molecular cloning and characterization of GPCR/CNS2, a novel G-protein coupled receptor which is highly expressed in the central nervous system. Soc Neurosci Abstr 24:1091, 1998 (abstract 432.11).